Posted
by
CowboyNealon Saturday February 17, 2007 @11:43AM
from the go-for-the-throat dept.

Ace905 writes "The National Institute of Allergy and Infectious Diseases announced Thursday that they had discovered a very promising 'weak spot' in the HIV virus. The HIV virus, a progenitor to full blown AIDS has eluded all attempts at a vaccine since it was discovered sometime in the 1970's. The major problem with developing a vaccine initially was isolating the virus. Conventional viruses are often defeated with existing drugs, or after being tested against new compounds. HIV has been unique, and staggering in it's ability to resist all attempts at treatment by mutating its own genetic code. HIV is able to resist, with great effectiveness, any drug or combination drug-therapy that is used against it."

...we'll release the virus into the population and all the fundamentalists who won't let their children take Guardasil and the AIDS vaccine will watch their genetic line dead-end! That's what you wanted to hear from this god-less progressive thinker, right? Silly trolls.

While I know (or at least I'm hoping) that the parent was a joke, the scary thing is that some people will think this way. AIDS is the big bogeyman of unprotected sex, but there are plenty of other nasty things you can get that have a lot less publicity. Yes, some won't kill you, some are treatable (though one should note that "treatable" and "curable" are two different things entirely), but the fact is that many of these are still very common [wikipedia.org] , Unpleasant [wikipedia.org], painful [wikipedia.org], repulsive [wikipedia.org], and still possibly disabling, [wikipedia.org]

The story that is referenced in the BBC news article refers to the structure of an antibody binding the gp120 surface glycoprotein of HIV. This has nothing to do with 'weak' DNA.
The reason why this is exciting is that the b12 region is relatively invariable, whereas most antibodies made against HIV bind variable regions of the surface glycoproteins that are prone to change from virus to virus as the genome is mutated. The majority of anti-HIV antibodies are therefore only useful against specific isolates and can be easily escaped by mutation. Antibodies against the b12 region are therefore potential vaccine candidates.

The Wikipedia article refers to the discovery of AIDS, which is the modern label applied to the clusters of disease cases with similar histories and symptoms which first identified (apparently) in 1981, although it seems some doctors and researchers were aware of unusual disease clusters for a few years leading up to that point. Recognition of AIDS as a disease led to researchers looking for a cause, which led to the subs

<groan>I made a mistake when I said it was discovered sometime in the 1970's. What I meant was, sometime in the 1970's the first few victims of the disease discovered they were deathly ill, and then died, after taking antibiotics and cold and flu medicine. Therefore, we have been fighting the disease since the first known infection and people 'discovered' it when they got it.

My write-up does imply it was 'identified by scientists' in the 1970's and that's not what I meant, but it was 4am.

Actually, when we started looking back for the origins of the disease, people started dying in largish numbers of a mysterious 'wasting disease' very similar to AIDS in Central Africa in the late 50's and early 60's.HIV antibodies were found in a blood sample of a British sailor who died in 1956 or '57, iirc, and there are scattered reports of a similar disease occurring in remote villages going as far back as the 30's, which is actually the suspected time frame for when the simian analog to HIV, SIV, first

Clearly you read neither my comment, which clearly refers to the article summary (a Slashdot feature) which incorrectly states that AIDS was discovered "sometime in the 1970's" nor the BBC article, which doesn't mention when AIDS was discoverd. I recalled from prior reading on the topic that AIDS was discovered in the 1980s. Wikipedia happened to get that one right, so I used it as the link. I also noticed that this particular Wikipedia article is extensively referenced.

You're partly right. It was in 1981 when the disease was discovered/recognized. It was 1982 when the CDC renamed the disease 'AIDS'. Before that, it was known as GRID. (Gay-Related Immune Deficiency) The causitive virus itself wasn't discovered until 1983, and wasn't renamed 'HIV' until 1986.

(Splitting hairs, I know, but it's early and I haven't had my coffee yet...)

I was surprised to learn from this article summary that the virus that causes AIDS was discovered "sometime in the 1970s", even though the syndrome hadn't even been observed by physicians until the early 1980s. I guess neither Gallo nor Montagnier should get credit for discovering LAV/HTLV/HIV, since they didn't isolate it and identify it as the probable cause of AIDS until around 1983.

The 1970s and 1980s were very different decades. The 1970s were the decade in which gay people came out of the closet

Antibodies against the b12 region are therefore potential vaccine candidates

b12 is a family of human antibodies that targets this viral protein gp120. gp120 is therefore the candidate for the vaccine. For vaccines we usually just inject viral protein(s) - as we would in this case - or a weak or dead form of the virus, and let the body make the antibodies (the b12 family in this case).

The talk about 'region' in this article probably refers to a site on the RNA of the virus: this region, encoding protein gp120, is not much changed by mutations - HIV codes genes in RNA since it's a retrovirus.

Also, since HIV targets the immune system, when someone has AIDS - the later stages of the disease in which the immune system is broken (targeted by HIV are T-cells) - vaccination may no longer work, since the immune system is no longer capable of producing antibodies, unless the T-cell count can be brought back to a level in which antibodies can be made.

so in the line of getting chicken pox to protect against small pox, what other viruses have gp120 or stimulate the production of b12 antibodies? Maybe a virus needs to be engineered: easy to beat, easy to spread, and provides immune systems with the right tools to potentially kill HIV.

yes, antibodies are produced by B-cells, but T-cells are required to enable B-cells to produce antibodies. In specific T-helper cells (CD4+) are targeted by HIV. from wiki:

When a B cell ingests a pathogen, it attaches parts of the pathogen's proteins to a class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T lymphocyte, which is compatible with similar structures on the cell membrane of a B lymphocyte. If the B cell and T cell structures match, th

Also, since HIV targets the immune system, when someone has AIDS - the later stages of the disease in which the immune system is broken (targeted by HIV are T-cells) vaccination may no longer work, since the immune system is no longer capable of producing antibodies, unless the T-cell count can be brought back to a level in which antibodies can be made.

Can you even use a vaccine after-the-fact? I thought the point of such was something akin to forewarning one's immune system ahead of time, training it on

Maybe they meant weak in the sense of 'weak key vulnerability'. Kind of a stretch, but in each case the 'protection' comes from something constantly changing to unique values, and there's an exploitable weakness produced by this not happening as it should. This is Slashdot, after all...

My question would also be: how do they test it in humans. I'd imagine they can combine infected and uninfected blood in a lab (with both vaccinated and non-vaccinated samples), but who's going to be the first live test? My guess would be a loving partner with an infected spouse (note that not all infections come from having sex with an infectee, there have been cases of tainted blood transfusions etc)

I suppose in the end people will get it just to be safe, as well, but the first while will be interesting.

It is highly improbable that the mutation rate in that part of the genome is lower. The b12 epitope overlaps with part of the CD4 binding site (the point of the Nature article referenced by the BBC report), it is thought to be functionally important for engaging the receptor, mutations in the region are therefore selected against. It is a weak spot in HIV's defense against the host, but not 'weak DNA' which suggests, at least to me, that the DNA is somehow brittle. At any rate, the weak spot is the accessib

Unfortunately the Pfizer receptor activates the Roche second messenger that has to go through the Merck gateway in the nucleus to bind to the Schering site on the DNA molecule. I doubt your drug will work...

I think there's already a cure for virginity... most people become immune naturally by the time they're twenty or so, but for a modest fee one can be cured at any local brothel.

Hey, if we eliminate virginity on a mass-scale, wont Muslims be pretty fucked? The supply of virgins has to be pretty robust to support the martyrdom industry. Wont somebody pleeease think of the Muslims?

Yeah, pretending that HIV "does" things intentionally to avoid vaccination is highly misleading. The problem is that viruses in general replicate quickly, and HIV in particular mutates very quickly from one generation to the next, while remaining viable. This lets an infection explore the parameter space of possible genotypes very fast. To be effective, a treatment needs to target some relatively stable feature of the virus, and eliminate the virus faster than the population can mutate away from that vul

Attributing human characteristics to posters like you is also a little bit of free license. Yes, the individual virii are able to change and adapt, because that is quite clearly what the article says. The composition of the 'shell' of the virus is sugar-based, with the compositional molecules constantly changing to prevent any specific, mass-produced biological defense from penetrating the shell. The one region in question, though, has the same composition regardless of the changing morphology around it,

This is about finding a stable surface protein on the surface of HIV which may be a good target for the production of an antigen which would elicit a stable immune response as a number of people have antibodies which target the same site. This has nothing to do with DNA, the submitter is just biologically illiterate.

Also, HIV is a retrovirus. For this family of viruses, their genome spends the majority of its time, and especially as an infectious particle, as RNA. It is only after infraction does its genome get replicated into DNA (through a process known as reverse transcription using a virally encoding RNA dependent DNA polymerase known as reverse transcriptase.) After being copied into DNA, the pro-virus is then inserted into the host's genome where RNA molecules are made (transcribed) to make viral proteins and full length copies of its genome for packaging into new infectious viral particles. This is a very import aspect of the virus' life-cycle and has many implications for some of the anti-retroviral therapies [wikipedia.org] on the market.

Damn, that sounds cool. Almost as exciting as computer stuff before I knew it. Maybe I should switch careers.Do they hire self-taught "bioengineering guru's" now like they used to hire software people back in the day?:P

Agreed! However, I learned about it 8 years ago as an undergrad. For some more interesting current research, have you heard about the link between retro-transposons (the epitome of the selfish gene -- the human genome DNA content is roughly 10% of these guy and ~50% transposons in general. Contrast this to the 1.5% of the human genome that encodes for proteins.) and retro-viruses? In a nut shell, retro-transposons and retro-viruses are the same critter, but retro-transposons have lost their env gene tha

Am I understanding correcftly when I think that that means that human DNA contains the "broken" dna of long gone viruses? And that a mutation in a human cell could potentially "fix" that dna and make the virus active again, potentially resurrecting a dangerous virus?

Anti viral drugs like acyclovir, valcyclovir, foscarnet, amantadine, etc at best slow down viral replication and limit the damage done by the virus. They do NOT eliminate the virus, nor do they "cure" a person's viral infection.

So how much has the life expectancy of an HIV+ individual increased since the use of combination antiviral drug therapy?

Life expectancy has increased a great deal, with one catch. You need 98% compliance to the treatment regimen. Be sure not to miss too many doses either now or 20 years from now, or you WILL develop AIDS.

why are governments around the world scrambling to stockpile tamiflu?

Because a drowning man will clutch at a straw, and it's better to be seen do

Fully 1/10th of sub-Saharan Africans are at risk. It's already created the largest ophan population since the Spanish Flu of 1918 (my great-granparents died in that one). I hope the antigen attack trials go quickly and smoothly, and the vaccine gets into circulation post-haste.

Well, since the body is sometimes too good at repelling foreign organisms, then a particular hard-to-repel virus might be useful if the dangerous effects could be removed. However, part of the strength and danger in HIV is that it targets and attacks yours defensive cells (a simplified explanation yes)... so how effective it would be without that part I don't know. However, one could in theory use a fairly benign virus-like organism to attack another, or such things.

You mean this vast plague upon mankind has a single point of failure? Wow! They really are close then. I suggest two possible courses of action from here: 1. Figure out how to plug a Powerbook into it, then type furiously. 2. Fly along the equator of the virus at top speed and fire into its exhaust port.

HIV is an RNA virus, NOT a DNA virus. Medical science knows a lot about treating DNA based viruses; But there are little to no treatments for RNA viruses. HIV has caused researchers to consider the RNA cycle, also. I wish them luck, and good hunting.

More specifically, HIV is a retrovirus. This means that as a standalone virus it contains RNA, but when it enters a cell, it uses reverse transcriptase to transcribe its RNA sequence into the equivalent DNA strand, which the cell's normal transcription/translation mechanism picks up and turns into the proteins and RNA that make the virus work.

It's the reverse transcription process that has a high error rate, which is why HIV's rate of mutation is so high. This results in a lot of nonviable DNA, but the virus takes years to work anyway. Eventually, some of these mutations result in a change in the proteins that are attacked by the various HIV drugs so that those drugs no longer work.

As for whether your statement about knowledge in treating various types of viruses is true or not, I don't know, but scientists do know an awful lot about HIV in particular. Each drug is meant to target a specific protein coded by the virus's genome. Being able to use drugs to target a "weak spot" (a spot that is brittle versus mutation) in the genome directly would be a major coup against the virus. This would be a great application for the grid computing mentioned in an earlier/. article. [slashdot.org]

My post was actually edited, I don't know how. I did put in an apostrophe, after the s - its' , which is a strange way i was taught to apostrophize possessive its'. Canadian English? Or a bad grade 1 teacher?

Figure 3 [nature.com] looks suspiciously like an atomic-level image showing the antibody b12 bound to the surface protein of the HIV virus. However, I'm not sure how able they are to make such an image perfectly accurately - the 1998 article they cited for the structure of gp120 said the structure was determined at a scale of 2.5 angstroms.

Figure 3a is gp120, with the parts bound to b12 colored green. It doesn't show the unnecessary parts of b12, because they're not the bits attacking gp120. It also shows the parts of the surface in contact with CD4, to show that b12 blocks cell entry. I don't know if you're expecting a photograph of a b12 molecule saying cheese to a disposable camera, but as far as I can tell it's definitely an atomic-level image of b12 attacking the surface of the virus. The BBC reported the fact perfectly accurately.

The grandparent is not correct. He said that viruses don't have DNA. He did not say that viruses don't generally have DNA if they also have RNA. Those statements are not equivalent, and he is not correct.

Only wish you were not serious, but sadly, apparently you are. Which raises the question how people actually can believe such utter and complete nonsense?

The HIV virus has not been seen by the eye or by light microscopy, as it is only 110 to 140 nanometer in diameter and below practical optical resolution. Although a group at the university of Chicago has been able to visualize something of its behavior by fluorescently tagging it. Of course then it is just a bright dot. However, HIV has been visualized n

> If you explore these areas, and find out that the HIV has actually never been seen, just the antibodies...

Uh, right. You know that the we've sequenced the HIV virus, right? Not only has it been sequenced, but it's been sequenced so many times that we can see the evolution of it's genetic code over time, and can tell which people infected which people. We can tell that the "Libyan seven" are innocent. We can tell that HIV evolved from SIV (the simian version of HIV) multiple times.

If you explore these areas, and find out that the HIV has actually never been seen, just the antibodies...supposedly...how on earth are scientists finding a vaccination or any treatment for an unknown/unseen virus? I wish I was kidding.

If you explore these areas, and find out that the HIV has actually never been seen

As other have pointed out this is simply not true. We have plenty of electron micrographs of HIV, not to mention the sequence of its genome. It is also a complete non-sequiter. We developed very effective vaccines against smallpox, rabies, and polio before we had pictures of them. Hell, the smallpox vaccine was invented before we had the germ theory of disease, let alone electron microscopes. It doesn't hurt to be able to vi

I should have added to my post...
Do no flame if you haven't seen the doc. I couldn't believe it myself...However I verified the facts and have questioned many experts on the subject.
Please show me a photo of HIV, and not a computer model guessing what it looks like. Please show me the original study showing that HIV is the cause of AIDS.
You won't be able to because they don't exist. Watch the show, and take the word of the experts who speak about it.
Don't shoot the messenger.
Also..this is only

Just because you don't like it, doesn't mean it's not used by everybody else - making it legitimate. I can't stand when people use the singular form of 'beer' to express how many bottles of beer they've drunk. When it comes in units, the plural has an S.

Language evolves. It is a very interesting topic. English itself is a kind of bastardized German, French, Latin, Scandinavian conglomerate that has evolved a set of "rules", that are not very consistent (if you have every studied Spanish or German seriously you know what I mean), and not really worth defending very hard.I correct my kids when they use ungramatical language because I want them to know the difference, but I certainly don't get bent out of shape if they speak that way to their peers; that woul